Introduction
In fall, as day length decreases, reproductive systems in many mammalian species that occupy temperate habitats "turn on." Testosterone levels rise in males, and females begin estrous cycling (“going into heat”). Gonadotropin-releasing hormone (GnRH) is part of a pathway that signals the body to produce sex hormones. GnRH is produced by the hypothalamus, a major organ in the brain. Without GnRH, very little estrogen, progesterone, or testosterone are made.

The aim of a GnRH vaccine is to bind to or “tie up” the GnRH produced within an animal's body so that it does not trigger reproduction. The vaccine induces the body to make antibodies against its own GnRH. To do this, GnRH is synthesized and hooked to a foreign protein. This new material (called a conjugate because it is made up of two components) looks like a giant new molecule that the animal's immune system has never encountered. As a result, when the GnRH vaccine is injected into the animal's body, the body's immune response neutralizes the hormone's function, resulting in infertility in both males and females.

As part of its program to develop tools for managing populations of overabundant wildlife species, NWRC scientists have developed a new GnRH immunocontraceptive vaccine (named GonaCon™) that shows great promise as a wildlife infertility agent. (Technical discussion on how GnRH immunocontraception works)

Two major obstacles had to be overcome during the development of this vaccine. First, a new adjuvant had to be developed (an adjuvant is a compound that improves the immune response, causing higher levels of antibodies). A replacement for the commonly used Freund’s adjuvant was needed because the U.S. Food and Drug Administration (FDA) objected to its use in wild animals. Accordingly, NWRC scientists developed a new adjuvant (called AdjuVac™) that is more effective than Freund’s adjuvant but lacks the negative side effects. (More on AdjuVac™ development)

The second major obstacle to the development of a new immunocontraceptive vaccine for wildlife was the need for a single-dose contraceptive, because of the impracticality of capturing free-ranging wild animals twice to vaccinate them. Previous contraceptive vaccines required at least two injections (an initial dose followed by a booster dose). Although it was originally developed as a two-injection contraceptive treatment, NWRC’s GnRH (gonadotropin-releasing hormone) vaccine was subsequently tested in a single-injection form that is much more practical as a field delivery system. Development of the single-injection vaccine was possible only because of the creation of AdjuVac™ adjuvant.

The usefulness of a single-shot immunocontraceptive vaccine depends, among other things, on the duration of the contraceptive effect that the vaccine produces. The combination of AdjuVac™ adjuvant and NWRC’s GnRH conjugate produces a much longer-lasting contraceptive effect than was produced by earlier efforts that combined Freund’s adjuvant with the (same) GnRH conjugate. (Technical discussion of NWRC vaccine conjugate design)

Pen and Field Studies of GonaCon™

Recent studies with free-ranging California ground squirrels, captive Norway rats, domestic and feral swine, wild horses, and white-tailed deer have demonstrated the efficacy of the single-shot GnRH vaccine as a contraceptive agent. Infertility among treated female swine and white-tailed deer, for example, has lasted up to five years without requiring a booster vaccination.

Recent studies have examined the practicality of administering GonaCon™ to free-ranging white-tailed deer as well as the efficacy, toxicity, and safety of the vaccine. Field studies in Maryland and New Jersey evaluated the efficacy of GonaCon™ as a contraceptive agent for free-ranging female white-tailed deer. In Maryland, an overpopulated deer herd on a completely fenced site was initially reduced in density by Wildlife Services sharpshooters at the request of property owners. Once the population size was reduced to a level that could be supported by the available habitat, contraception was applied to adult females. Forty–three does were captured, marked, and released at their capture sites during July 2004. Of those does, 28 were injected with GonaCon™ vaccine, and 15 were maintained as unvaccinated control animals. Data show the vaccine to be 88 percent effective the first year and 47 percent effective the second year in treated deer.

In July 2005, a similar field study involving another 28 deer was started in Morris County, NJ, that showed 67 percent effectiveness the first year and 48 percent effectiveness the second year. NWRC scientists collaborated on this study with White Buffalo, Inc., a non-profit, Connecticut-based research organization dedicated to conserving ecosystems through wildlife population control.

NWRC also collaborated with Pennsylvania State University to conduct studies required by EPA on the toxicity and safety of GonaCon™ in captive deer. Responses of treated and control groups of deer were compared via blood and tissue analyses. Data showed no differences between treatment and control groups.

EPA Registration of GonaCon™

In 2006, the regulatory authority for contraceptives for wildlife and feral animals was moved from the U.S. Food and Drug Administration to the U.S. Environmental Protection Agency (EPA).

GonaCon™ is not yet commercially available. USDA plans to submit data to the EPA in early 2009 to support a registration for the use of GonaCon™ in managing white-tailed deer populations, with registration being granted between 12-18 months following submission. NWRC scientists anticipate that GonaCon™ will be registered by the EPA as a “Restricted Use” product, probably for use by state or federal wildlife or natural resource management personnel or persons working under their authority. Once the initial registration is granted, it is likely that NWRC will pursue the registration for other species, such as prairie dogs, ground squirrels, feral swine and feral dogs.

Advantages of GnRH

NWRC scientists are hopeful that the GnRH vaccine will soon be approved for use for wildlife fertility control. GnRH vaccines have an advantage over PZP because they prevent eggs from being released from the ovaries, thereby eliminating estrus and some undesirable behaviors (e.g., bucks chasing does across roads) associated with it. In addition, GnRH vaccine has promise for reducing or eliminating certain undesirable behaviors in companion animals. For example, fighting, scent-marking, caterwauling, and wandering by cats, and unruly behavior in horses, could be reduced by GnRH vaccine because the vaccine indirectly blocks the production of sex hormones (e.g., estrogen and testosterone) which contribute to the expression of such behaviors.

The single-shot, multi-year GonaCon™ vaccine will be a useful technique for the management of certain enclosed or urban/suburban wildlife populations, such as deer. GonaCon™ still has limitations, however, especially the need to capture and inject each animal.